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Jan Nilsson

Professor

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Low Levels of Circulating CD4+FoxP3+ T Cells Are Associated With an Increased Risk for Development of Myocardial Infarction But Not for Stroke.

Author

  • Maria Wigren
  • Harry Björkbacka
  • Linda Andersson
  • Irena Ljungcrantz
  • Gunilla Nordin Fredrikson
  • Margaretha Persson
  • Carl Bryngelsson
  • Bo Hedblad
  • Jan Nilsson

Summary, in English

OBJECTIVE:

Regulatory T cells (Tregs) protect against atherosclerosis in experimental models, but their association with cardiovascular disease in humans remains to be elucidated. The aim of the present study was to determine whether circulating Tregs predict the development of acute cardiovascular events in humans.



METHODS AND RESULTS:

The study cohort consisted of a random sample of participants (n=700), aged 68 to 73 years, from the Malmo Diet and Cancer Study. Mononuclear leukocytes, stored at -140°C at the baseline investigation in 1991.1994, were thawed and Tregs, defined by the expression of FoxP3 in CD4+ T cells, were analyzed by flow cytometry. There was no detectable loss of cells during storage, and the viability of thawed leukocytes was 95%. A low fraction of both CD4+FoxP3+ and CD4+CD25+FoxP3+ T cells was associated with a higher release of proinflammatory cytokines from activated mononuclear leukocytes, and this association was strongest for CD4+FoxP3+ cells. Eighty-four coronary events and 66 strokes were registered during follow-up until December 31, 2008. In a Cox proportional hazard regression model adjusting for major risk factors, low levels of baseline CD4+FoxP3+ T cells were associated with an increased risk for the development of acute coronary events but not stroke. There were no associations between CD4+CD25+FoxP3+ T cells and development of an acute coronary event or stroke.



CONCLUSIONS:

This study provides prospective evidence for the role of Tregs in the development of myocardial infarction. The findings are in accordance with previous experimental studies and provide clinical support for a protective role of Tregs in atherosclerosis. The lack of association between Tregs and stroke may reflect the more heterogeneous cause of this disease.

Department/s

  • Cardiovascular Research - Immunity and Atherosclerosis
  • Internal Medicine - Epidemiology
  • Cardiovascular Research - Epidemiology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2012

Language

English

Pages

2000-2007

Publication/Series

Arteriosclerosis, Thrombosis and Vascular Biology

Volume

32

Issue

8

Document type

Journal article

Publisher

Lippincott Williams & Wilkins

Topic

  • Cardiac and Cardiovascular Systems

Keywords

  • immune system
  • coronary disease
  • lymphocytes
  • carotid arteries

Status

Published

Research group

  • Cardiovascular Research - Immunity and Atherosclerosis
  • Internal Medicine - Epidemiology
  • Cardiovascular Research - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1524-4636